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Neurotensin agonist attenuates nicotine potentiation to cocaine sensitization.

Fredrickson P, Boules M, Stennett B, Richelson E - Behav Sci (Basel) (2014)

Bottom Line: Tobacco usage typically precedes illicit drug use in adolescent and young adult populations.Neurotensin (NT) is a 13-amino acid neuropeptide that modulates dopamine, acetylcholine, glutamate, and GABA neurotransmission in brain reward pathways.Behavior was recorded with the use of activity chambers.

View Article: PubMed Central - PubMed

Affiliation: Neuropsychopharmacology Laboratory, Mayo Foundation for Medical Education and Research Mayo Clinic Florida, 4500 San Pablo road, Jacksonville, FL 32224, USA; E-Mails: boules.mona@mayo.edu (M.B.); richel@mayo.edu (E.R.); bastenn@gmail.com (B.S.).

ABSTRACT
Tobacco usage typically precedes illicit drug use in adolescent and young adult populations. Several animal studies suggest nicotine increases the risk for subsequent cocaine abuse, and may be a negative prognostic factor for treatment of cocaine addiction; i.e., a "gateway drug". Neurotensin (NT) is a 13-amino acid neuropeptide that modulates dopamine, acetylcholine, glutamate, and GABA neurotransmission in brain reward pathways. NT69L, a NT(8-13) analog, blocks behavioral sensitization (an animal model for psychostimulant addiction) to nicotine, and nicotine self-administration in rats. The present study tested the effect of NT69L on the potentiating effects of nicotine on cocaine-induced locomotor sensitization. Male Wistar rats were injected daily for seven days with nicotine or saline (control) followed by four daily injections of cocaine. NT69L was administered 30 min prior to the last cocaine injection. Behavior was recorded with the use of activity chambers. Subchronic administration of nicotine enhanced cocaine-induced behavioral sensitization in Wistar rats, consistent with an hypothesized gateway effect. These behavioral effects of cocaine were attenuated by pretreatment with NT69L. The effect of the neurotensin agonist on cocaine sensitization in the nicotine treated group indicated a possible therapeutic effect for cocaine addiction, even in the presence of enhanced behavioral sensitization induced by nicotine.

No MeSH data available.


Related in: MedlinePlus

Effects of NT69L on locomotor activity in rats exposed to nicotine and cocaine. Male Wistar rats (n = 4-16 per group) were injected twice daily for seven days with nicotine (0.35 mg/kg s.c.) or saline control followed by four daily injections of cocaine (20 mg/kg i.p.). Cocaine challenge (20 mg/kg i.p.) was administered 48 h after the last cocaine injection. NT69L (1 mg/kg i.p.) was administered 30 min prior to cocaine injection on test days. Behavior was recorded with the use of activity chambers. (a) Effect of chronic nicotine injection on locomotor activity; (b) Effect of NT69L on cocaine-induced locomotor sensitization; (c) Effect of chronic nicotine pretreatment on subsequent cocaine sensitization; (d) Effect of NT69L on expression of nicotine-enhanced cocaine sensitization and cocaine challenge.
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behavsci-04-00042-f002: Effects of NT69L on locomotor activity in rats exposed to nicotine and cocaine. Male Wistar rats (n = 4-16 per group) were injected twice daily for seven days with nicotine (0.35 mg/kg s.c.) or saline control followed by four daily injections of cocaine (20 mg/kg i.p.). Cocaine challenge (20 mg/kg i.p.) was administered 48 h after the last cocaine injection. NT69L (1 mg/kg i.p.) was administered 30 min prior to cocaine injection on test days. Behavior was recorded with the use of activity chambers. (a) Effect of chronic nicotine injection on locomotor activity; (b) Effect of NT69L on cocaine-induced locomotor sensitization; (c) Effect of chronic nicotine pretreatment on subsequent cocaine sensitization; (d) Effect of NT69L on expression of nicotine-enhanced cocaine sensitization and cocaine challenge.

Mentions: Acute and 7 daily treatments twice per day with nicotine (0.35 mg/kg s.c.) significantly (F4,46 = 11.339, P < 0.001) increased locomotor activity. Injection of nicotine significantly increased locomotor activity as compared to baseline and saline control, P < 0.05. Repeated injection of nicotine further increased locomotor activity as compared to acute injection (P < 0.03), results that are indicative of sensitization (Figure 2a).


Neurotensin agonist attenuates nicotine potentiation to cocaine sensitization.

Fredrickson P, Boules M, Stennett B, Richelson E - Behav Sci (Basel) (2014)

Effects of NT69L on locomotor activity in rats exposed to nicotine and cocaine. Male Wistar rats (n = 4-16 per group) were injected twice daily for seven days with nicotine (0.35 mg/kg s.c.) or saline control followed by four daily injections of cocaine (20 mg/kg i.p.). Cocaine challenge (20 mg/kg i.p.) was administered 48 h after the last cocaine injection. NT69L (1 mg/kg i.p.) was administered 30 min prior to cocaine injection on test days. Behavior was recorded with the use of activity chambers. (a) Effect of chronic nicotine injection on locomotor activity; (b) Effect of NT69L on cocaine-induced locomotor sensitization; (c) Effect of chronic nicotine pretreatment on subsequent cocaine sensitization; (d) Effect of NT69L on expression of nicotine-enhanced cocaine sensitization and cocaine challenge.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4219249&req=5

behavsci-04-00042-f002: Effects of NT69L on locomotor activity in rats exposed to nicotine and cocaine. Male Wistar rats (n = 4-16 per group) were injected twice daily for seven days with nicotine (0.35 mg/kg s.c.) or saline control followed by four daily injections of cocaine (20 mg/kg i.p.). Cocaine challenge (20 mg/kg i.p.) was administered 48 h after the last cocaine injection. NT69L (1 mg/kg i.p.) was administered 30 min prior to cocaine injection on test days. Behavior was recorded with the use of activity chambers. (a) Effect of chronic nicotine injection on locomotor activity; (b) Effect of NT69L on cocaine-induced locomotor sensitization; (c) Effect of chronic nicotine pretreatment on subsequent cocaine sensitization; (d) Effect of NT69L on expression of nicotine-enhanced cocaine sensitization and cocaine challenge.
Mentions: Acute and 7 daily treatments twice per day with nicotine (0.35 mg/kg s.c.) significantly (F4,46 = 11.339, P < 0.001) increased locomotor activity. Injection of nicotine significantly increased locomotor activity as compared to baseline and saline control, P < 0.05. Repeated injection of nicotine further increased locomotor activity as compared to acute injection (P < 0.03), results that are indicative of sensitization (Figure 2a).

Bottom Line: Tobacco usage typically precedes illicit drug use in adolescent and young adult populations.Neurotensin (NT) is a 13-amino acid neuropeptide that modulates dopamine, acetylcholine, glutamate, and GABA neurotransmission in brain reward pathways.Behavior was recorded with the use of activity chambers.

View Article: PubMed Central - PubMed

Affiliation: Neuropsychopharmacology Laboratory, Mayo Foundation for Medical Education and Research Mayo Clinic Florida, 4500 San Pablo road, Jacksonville, FL 32224, USA; E-Mails: boules.mona@mayo.edu (M.B.); richel@mayo.edu (E.R.); bastenn@gmail.com (B.S.).

ABSTRACT
Tobacco usage typically precedes illicit drug use in adolescent and young adult populations. Several animal studies suggest nicotine increases the risk for subsequent cocaine abuse, and may be a negative prognostic factor for treatment of cocaine addiction; i.e., a "gateway drug". Neurotensin (NT) is a 13-amino acid neuropeptide that modulates dopamine, acetylcholine, glutamate, and GABA neurotransmission in brain reward pathways. NT69L, a NT(8-13) analog, blocks behavioral sensitization (an animal model for psychostimulant addiction) to nicotine, and nicotine self-administration in rats. The present study tested the effect of NT69L on the potentiating effects of nicotine on cocaine-induced locomotor sensitization. Male Wistar rats were injected daily for seven days with nicotine or saline (control) followed by four daily injections of cocaine. NT69L was administered 30 min prior to the last cocaine injection. Behavior was recorded with the use of activity chambers. Subchronic administration of nicotine enhanced cocaine-induced behavioral sensitization in Wistar rats, consistent with an hypothesized gateway effect. These behavioral effects of cocaine were attenuated by pretreatment with NT69L. The effect of the neurotensin agonist on cocaine sensitization in the nicotine treated group indicated a possible therapeutic effect for cocaine addiction, even in the presence of enhanced behavioral sensitization induced by nicotine.

No MeSH data available.


Related in: MedlinePlus